Methods for the biosynthesis of derivatives of 4-hydroxy-2-ketobutyrate by fermentation, where the microorganism metabolically transforms a simple source of carbon into derivatives of 4-hydroxy-2-ketobutyrate are known in the art. Such derivatives of 4-hydroxy-2-ketobutyrate are in particular 1,3-propanediol or 2,4-dihydroxybutyrate. The latter is a precursor of methionine hydroxyl analogue (MHA).
Preparation of 1,3-propanediol from 4-hydroxy-2-ketobutyrate by fermentation is well disclosed in WO 2010/076324 and WO 2012/004247 patent applications which are incorporated herein by reference.
Preparation of 2,4-dihydroxybutyrate from 4-hydroxy-2-ketobutyrate by fermentation is well disclosed in WO 2014/009435 patent application incorporated herein by reference.
In these pathways of production of 1,3-propanediol or 2,4-dihydroxybutyrate, 4-hydroxy-2-ketobutyrate is obtained by the oxidative deamination of L-homoserine.
It is particularly known from these applications to improve the metabolic pathway to favour the production of L-homoserine and to limit the usual metabolic pathways using L-homoserine as a substrate, like for its conversion into L-threonine.
In patent applications WO 2010/076324 and WO 2012/004247, conversion of 4-hydroxy-2-ketobutyrate into 1,3-propanediol or into 2,4-dihydroxybutyrate are well described. The pathway for 1,3-propanediol production from 4-hydroxy-2-ketobutyrate comprises two steps after the conversion of L-homoserine into 4-hydroxy-2-ketobutyrate:                a first step of converting 4-hydroxy-2-ketobutyrate into 3-hydroxypropionaldehyde, and        a second step of converting 3-hydroxypropionaldehyde into 1,3-propanediol.        
For 2,4-dihydroxybutyrate production, L-homoserine is converting into 4-hydroxy-2-ketobutyrate and then 4-hydroxy-2-ketobutyrate is converting into 2,4-dihydroxybutyrate as disclosed in patent application WO2014/009435.
Even if main steps of these pathways are well described, the step of converting L-homoserine into 4-hydroxy-2-ketobutyrate is a limiting step.
The inventors have now found that this step can be improved by using a mutant glutamate dehydrogenase converting L-homoserine into 4-hydroxy-2-ketobutyrate by deamination.